The clinical data of a case of diabetic ketoacidosis with FOXP3 mutation identified by genetic test were collected and summarized. The follow-up results and clinical characteristics of 18 months after hematopoietic stem cell transplantation were analyzed. The male patient was 3 years and 5 months old. At the age of 5 months, the patient was diagnosed as diabetic ketoacidosis due to mental malaise and vomiting, followed by severe diarrhea, repeated eczema, and nephrotic syndrome, which was confirmed as IPEX syndrome due to FOXP3 gene mutation by genetic test. In August 2018, hematopoietic stem cell transplantation was carried out in the Hematology Department of our hospital. During 18 months of follow-up, the patients′ autoimmune status was ameliorated, no new autoimmune diseases appeared, the blood glucose control was significantly improved, and the insulin dosage was significantly reduced.

Kabuki syndrome(KS),also called kabuki make-up syndrome,is characterized by backward growth retardation,skeletal developmental delay,major facial dysmorphic features,multi-organ abnormalities and abnormal dermatoglyphic pattern and mild or moderate mental retardation.For the molecular genetic pathogenesis of KS,KTM2D and KDM6A gene mutations have been identified as pathogenic genes of KS,which regulate the gene expression through chromatin remodelling and histone modification.At present,the etiology and pathogenesis of KS are still unknown.There is no useful biochemical index and standard radiographic findings for the diagnosis of KS.Molecular genetic diagnosis is still to be explored.Currently,the diagnosis of KS is mainly based on five cardinal manifestations:a peculiar face,skeletal anomalies,dermatoglyphic abnormalities,mild to moderate mental retardation and postnatal growth deficiency.For these patients,it can reach a better prognosis the by clinical early detection,early diagnosis,early intervention,as well as improving the growth level,symptomatic treatment,active prevention and treatment of complications as far as possible.

OBJECTIVE: To analyze the clinical characteristics and genetic variation in a child with acrodysostosis type 2. METHODS: The child has undergone history taking and physical examination. Genome DNA was extracted from peripheral blood samples from him and his parents. High-throughput sequencing was carried out. The result was verified by Sanger sequencing. RESULTS: The 8-year-old boy presented with midface hypoplasia, hypertelorism, prominent nasal bridge, small and upturned nostrils, broad thumb and great toes, and brachydactyly of remaining fingers and toes. Genetic testing revealed that the child has carried a heterozygous c.1813T>C (p.Tyr605His) missense mutation of the PDE4D gene. The same mutation was not found in either parent and was unreported previously. CONCLUSION The child was diagnosed with acrodysostosis type 2 due to the novel mutation of the PDE4D gene.

OBJECTIVE: To explore the clinical characteristics and genetic basis for an infant featuring combined pituitary hormone deficiency. METHODS: Clinical data and results of DNA sequencing of the child were analyzed. RESULTS: The 10-month-old male infant presented with recurrent hypoglycemia, extremely poor appetite and constipation, and severe growth retardation from 2 months on, in addition with pituitary hormone deficiency involving growth hormone, thyroid stimulating hormone, and prolactin. Next generation sequencing revealed a novel heterozygous c.767-769del (p.Glu256del) variant of the POU1F1 gene in the patient. CONCLUSION The patient was diagnosed with combined pituitary hormone deficiency due to the POU1F1 gene variant, for which replacement therapy including thyroxine and growth hormone was provided. Hypoglycemia is unusual in patients carrying POU1F1 gene variants and requires close attention in clinical practice. For children with multiple pituitary hormone deficiency, genetic testing should be recommended to determine the cause.

OBJECTIVE: To explore the clinical and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene. METHODS: Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents. RESULTS: The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent. CONCLUSION The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.
Child ; Filamins/genetics* ; Forehead/abnormalities* ; Humans ; Infant ; Male ; Osteochondrodysplasias/genetics* ; Phenotype ; Whole Exome Sequencing

OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
Child ; Humans ; China ; Dwarfism ; Genetic Testing ; Heterozygote ; Syndrome

Turner syndrome（TS），a condition among females with a karyotype containing one X chromosome and complete or partial absence of the second sex chromosome，affects 20～50 in 100 000 newborn girls. Congenital or acquired cardiovascular diseases are present in about half of patients with TS. The congenital defects occur in about 25%～50% of TS patients；aortic dilatation as an important risk factor for aortic dissection is common in adult patients with TS. Furthermore，arrhythmias are found more frequently in patients with TS. A higher prevalence of hypertension in children and adolescents with TS has also been reported，and the application of 24h ambulatory blood pressure monitoring may facilitates the diagnosis of hypertension among these children and adolescent.Thus，active health education，correct follow-up and timely intervention are crucially needed.

OBJECTIVE: To explore the clinical characteristics and genetic basis of a child with Teebi hypertelorism syndrome 1 (TBHS1). METHODS: A child with TBHS1 who was admitted to the Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine on July 13, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 13-year-old male, had manifested delayed growth and development. WES results revealed that he has harbored a heterozygous c.1244A>G variant of the SPECC1L gene, which was verified to be de novo in origin. The variant has not been included in the HGMD and gnomAD databases. As predicted by online software including PolyPhen-2, SIFT, and Mutation Taster, the variant may affect the function of protein domain. And PyMOL software has predicted that the structural stability of SPECC1L protein (p.Gln415Arg) might be reduced. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PM6+PM1+PP4+PM2_Supporting+PP3). CONCLUSION The heterozygous c.1244A>G variant of the SPECC1L gene probably underlay the TBHS1 in this child. Above finding has expanded the genotypic and phenotypic spectrum of the SPECC1L gene and provided a basis for the clinical diagnosis of this child.
Adolescent ; Humans ; Male ; China ; Computational Biology ; Genomics ; Genotype ; Mutation

Alstrom syndrome(ALMS)is a rare autosomal recessive disorder involving multiple systems.The main clinical manifestations include nystagmus, hearing loss, obesity, insulin resistance, type 2 diabetes, dilated cardiomyopathy, etc.Primary cilia are key organelles.ALMS is classified as a ciliopathy, mainly related to the mutation of ALMS1 gene which affects cilia function, but the specific mechanism remains unclear.At present, the diagnosis of ALMS mainly relies on clinical manifestations and gene sequencing.There are no specific and effective treatment methods except for symptomatic treatment, but early diagnosis and intervention can delay disease progression and improve patients′ quality of life.This article reviews recent advances in the pathogenesis, diagnosis, and treatment of ALMS.

Objective:To explore the differences of microenviroment between peri-implant tissue and oral mucosal tissue.Methods:The gene chip data GSE43744 was downloaded from the GEO database,bioinformatics tools were used to analyze the differentially ex-pressed genes between the peri-implant tissue and normal oral mucosal tissue in rat.Results:1315 differentially expressed important genes,including 797 upregulated genes and 518 downregulated genes,were screened out.Gene enrichment analysis showed that com-pared with normal oral mucosal tissue,the gene expression of innate immune activity,cell activation,inflammatory response,and func-tional expression related to external and bacterial stimuli in peri-implant tissue were significantly upregulated,while that of extracellular matrix tissue,adhesion,extracellular matrix polysaccharides,response to mechanical stimuli and response to toxic substances was sig-nificantly downregulated.Meanwhile,multiple molecular functions and biological pathways related to T cells were highly expressed,which may play an important role in the peri-implant microenvironment.In addition,PPI network was constructed,and screened 7 core genes including FCER1G,TYROBP,PTPRC,ITGB2,AIF1,EMR1 and RAC2,which may be target genes for studying peri-implant microenvironment.Conclusion:There is a significant difference of microenvironment characteristics between peri-implant tissue and o-ral mucosa.The target genes screened using PPI network may be the key to future research on the peri-implant microenvironment.